PT1609362E - Non-systemic control of parasites - Google Patents

Abstract

Use of agonists and antagonists of nicotinic acetylcholine receptor (A) of insects for non-systemic combating of parasitic insects (fleas, lice and flies) on humans and animals. Independent claims are also included for: an agent and molded articles for non-systemic combating of parasitic insects on humans and animals comprising (A). ACTIVITY : Antiparasitic; Plant Protectant; Insecticide. MECHANISM OF ACTION : Nicotinic acetylcholine receptor agonist; Nicotinic acetylcholine receptor antagonist.

Description

DESCRIPTION " NON-SYSTEMIC FIGHT AGAINST PARASITES " The present invention relates to non-systemic fighting against parasitic insects of the flea, lice and fly group in humans and animals by means of agonists or antagonists of insect nicotinergic acetylcholine receptors, namely imidacloprid.

The insect nicotinergic acetylcholine receptor agonists or antagonists are known. To these belong the nicotinyl insecticides and most particularly the chloronicotinyl insecticides. It is also known that these compounds act excellently against plant-injurious insects. The systemic effect of these compounds on plants against plant-injurious insects is also known. From PCT application WO 93/24002 it is known that specific derivatives of 1- [N- (halo-3-pyridylmethyl) -N-methylamino-1-alkylamino-2-nitroethylene are suitable for systemic application against fleas in animals households. In this type of application, the active substance is administered orally or parenterally to the domestic animal, e.g. ex. by injection, and thus enters the bloodstream of the domestic animal. Fleas receive the active substance later, when they suck blood. According to WO 93/24002, the non-systemic form of the application is not suitable for the control of fleas in domestic animals.

Surprisingly, it has now been found that precisely imidacloprid in admixture with synthetic pyrethroids, flumethrin or permethrin, is particularly suitable for non-systemic fighting against parasitic insects such as fleas, lice or flies in humans and animals.

The insect nicotinergic acetylcholine receptor agonists or antagonists are known e.g. ex. from the European Patent Publication Nos 464830, 428941, 425978, 386565, 383091, 375907, 364844, 315826, 259738, 254859, 235725, 212600, 192060, 163855, 154178, 136636, 303570, 302833, 306696, 189972, 455000, 135956, 471372, 302389; German Patent Application Publication Nos 3639877, 3712307; of published Japanese patent applications 03220176, 02207083, 63307857, 63287764, 03246283, 049371, 03279359, 03255072; U.S. patent applications 5034524, 4948798, 4918086, 5039686, 5034404; PCT Applications No. WO 91/17659, 91/4965; French Patent Application No. 2611114; Brazilian patent application Ser. No. 8803621. Expressed herein is made reference to the methods, processes, formulas and definitions described in those publications, as well as to the individual preparations and compounds described therein. Imidacloprid (1 - [(6-chloro-3-pyridinyl) methyl] -N-nitro-2-imidazolidinium) has the following formula

The active substance is suitable for favorable toxicity in warm-blooded animals for the control of parasitic insects arising in humans and on the holding and rearing of domestic and commercial animals as well as zoo animals, of experimentation and company. In this case, it is active against all or some of the stages of parasite development, as well as against resistant and normally sensitive types of parasites.

They belong to parasites: from the order of Anoplura, p. ex. Haematopinus spp., Linognathus spp., Solenopotes spp., Pediculus spp., Pthirus spp. ; from the order of the Mallophaga, p. ex. Trimenopon spp., Menopon spp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicola spp., Damalinea spp., Bovicola spp .; from the order of the Diptera, p. ex. Chrysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp., Haematobosca spp., Haematobia spp., Stomoxys spp., Fannia spp., Glossina spp., Lucilia spp., Calliphora spp., Auchmeromyia spp. , Cordylobia spp., Cochliomyia spp., Chrysomyia spp., Sarcophaga spp.

Wohlfartia spp., Gasterophilus spp., Oesteromyia spp., Oedemagena spp., Hypoderma spp., Oestrus spp., Rhinoestrus spp., Melophagus spp., Hippobosca spp.

From the order of the Siphonaptera, p. ex. Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp. The effect against Siphonaptera, particularly against fleas, is particularly emphasized. The following target animals are preferably indicated:

To the utilitarian and creative animals belong the mammals, like p. ex. cows, horses, sheep, pigs, goats, camels, Asian buffalo, donkeys, rabbits, deer, reindeer, fur animals, ex. visons, chinchillas, raccoons, birds, such as p. ex. chickens, geese, turkeys, ducks.

Experimental and laboratory animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.

Dogs and cats belong to pets. The application may be effected either prophylactically or therapeutically. The application of the active substances is carried out either directly or in the form of suitable skin preparations, by treatment of the enclosure, or with the aid of shaped bodies containing the active substance, ex. strips, plates, straps, collars, ear tags, member straps, marking devices. The dermal application happens p. ex. in the form of bathing, soaking (spraying), spraying, pouring (pouring or pouring on the spot), washing, shampooing, spraying, dusting. Suitable preparations are: solutions or concentrates for administration upon dilution, solutions for use on the skin, pour-on formulations, gels; emulsions and suspensions for dermal application, as well as semi-solid preparations; formulations in which the active substance is processed in an ointment base, or in an oil-in-water or water-in-oil emulsion base; solid preparations, such as powders, molded bodies containing active substance.

Solutions for use on the skin are instilled, scattered, scrubbed, spilled, sprayed or applied by immersion (dip), bath or lavage.

The solutions are prepared by solubilisation of the active substance in a suitable solvent and additives such as solubilizing agents, acids, bases, buffer salts, antioxidants, preservatives are optionally added.

Suitable solvents are: physiologically acceptable solvents, such as water, alcohols, such as ethanol, butanol, benzyl alcohol, glycerol, hydrocarbons, propylene glycol, polyethylene glycols, N-methyl pyrrolidone, as well as mixtures thereof.

The active substances may also optionally be dissolved in physiologically acceptable vegetable or synthetic oils.

Solubilizing agents are indicated: solvents which promote the solution of the active substance in the main solvent or prevent its precipitation. Examples are polyvinylpyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan ester.

Preservative agents are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.

It may be advantageous to add thickening agents in the preparation of the solutions. Thickening agents are: inorganic thickening agents such as bentonite, colloidal silicic acid, aluminum monostearate, organic thickening agents, such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.

The gels which are applied or spread onto the skin are prepared by mixing the solutions, which have been prepared as described above, with the amount of thickening agent required to produce a clear mass with ointment-like consistency. As thickening agent the thickening agents indicated above are employed.

Spill formulations are poured or sprayed over limited areas of the skin, where the active substance is distributed over the body surface.

Pour-on formulations are prepared by solubilising, suspending or emulsifying the active substance in suitable skin-compatible solvents or solvent mixtures. Additional auxiliary substances, such as colorants, antioxidants, light-protecting agents, adhesive agents, are optionally added.

Suitable solvents are water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols, such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, butyl benzoate, ethers such as alkylene glycol alkyl ethers, such as diethyleneglycol monobutyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-1,3- dioxolane.

Dyes are all authorized dyes for application to animals, which can be dissolved or suspended.

Auxiliary agents are also spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are sulfites or metabisulfites, such as potassium metabisulfite, ascorbic acid, butyl hydroxy toluene, butyl hydroxyanisole, tocopherol.

Light-protecting agents are e.g. ex. substances of the class of benzophenones or nonvantisolic acid.

Adhesive agents are e.g. ex. cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

The emulsions are either water-in-oil or oil-in-water type.

They are prepared by solubilising the active ingredient either in the hydrophobic phase or in the hydrophilic phase and is homogenized with the solvent of the other phase with the aid of suitable emulsifiers and optionally additional auxiliaries such as colorants, absorption promoting substances, preservatives, antioxidants, light-protecting agents, viscosity-increasing substances.

Hydrophobic phase (oils) are indicated: paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic acid / capric acid, triglyceride mixture with fatty acids vegetables of C8-i2 chain length or other specially selected fatty acids, partial mixtures of saturated or unsaturated glycerides, optionally also hydroxyl group containing fatty acids, mono and diglycerides of the C8 / C10 fatty acids. Fatty acid esters, such as ethyl stearate, di-n-butyryl adipate, hexyl laureate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of C 16 -C 18 chain length, myristate isopropyl palmitate, esters of caprylic / capric acids of saturated fatty alcohols of C12 -C18 chain length, isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, fatty acid esters of such as dibutyl phthalate, diisopropyl adipate, mixtures of esters analogous to the latter, among others, fatty alcohols, such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol, oleyl alcohol. Fatty acids, such as p. ex. oleic acid and mixtures thereof.

As the hydrophilic phase are indicated: water, alcohols as e.g. ex. propylene glycol, glycerol, sorbitol and mixtures thereof. Emulsifiers are indicated as: non-ionogenic surfactants, e.g. ex. polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether; ampholytic surfactants such as di-Na-N-lauryl β-iminodipropionate or lecithin; surfactants active in anionic terms, such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / monoalkanolamine salt of mono / dialkylpolyglycol ether phosphoric acid ester; cationically active surfactants, such as cetyltrimethylammonium chloride. Additional auxiliaries include viscosity-increasing substances and emulsion stabilizing substances, such as carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, copolymers of ether methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silicic acid or mixtures of the substances mentioned.

The suspensions are prepared by suspending the active substance in a carrier liquid, optionally with the addition of additional auxiliaries, as wetting agents, colorants, absorption promoting substances, preservatives, antioxidants, light-protecting agents. All homogeneous solvents and solvent mixtures are indicated as carrier liquids. Wetting agents (dispersing agents) are indicated as the surfactants mentioned above. Additional auxiliaries are those mentioned above.

Semi-solid preparations for dermal administration are distinguished from the suspensions and emulsions described above only by their higher viscosity.

For the preparation of solid preparations, the active substance is mixed with suitable carrier substances, optionally with addition of auxiliary substances, and is brought to the desired shape. All physiologically acceptable inert solids are indicated as carrier substances. As such they serve the inorganic and organic substances. Inorganic substances are e.g. ex. cooking salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicic acids, aluminas, precipitated or colloidal silicon dioxide, phosphates.

Auxiliaries are preservatives, antioxidants, dyes, which have already been mentioned above.

Suitable additional auxiliaries are slip agents and lubricants, such as e.g. ex. magnesium stearate, stearic acid, talc, bentonite.

The ready-to-use preparations contain the active substance in concentrations of 1 ppm - 20 percent by weight, preferably 0.01-10 percent by weight.

The preparations which are diluted prior to application contain the active substance in concentrations of 0.5-90 weight percent, preferably 1 to 50 weight percent.

In general, it has been found to be advantageous to administer amounts of about 0.5 to about 50 mg, preferably 1 to 20 mg, of active ingredient per kg of body weight per day to achieve effective results. The application through molded bodies is particularly emphasized. Molded bodies are, among others, collars, pendants for medallions, ear tags, bands for attachment to limbs or body parts, strips and adhesive sheets, removable sheets. Collars and medallions are particularly emphasized.

For the preparation of the molded bodies are considered thermoplastic and flexible thermoplastic synthetic materials, as well as thermoplastic elastomers and elastomers. As such are indicated the polyvinyl resins, polyurethanes, polyacrylates, epoxy resins, cellulose, cellulose derivatives, polyamides and polyesters which are sufficiently compatible with the active substance indicated above. The polymers must have sufficient strength and flexibility not to crack during molding or to become brittle. They should be of sufficient consistency to be stable against normal wear and tear. In addition, the polymers should allow sufficient migration of the active substance to the surface of the molded body. The polyvinyl resins include the polyvinyl halides, such as polyvinyl chloride, polyvinyl chloride-vinyl acetate and polyvinyl fluoride; polyacrylate and polymethacrylate esters, such as polymethylacrylate and polymethylmethacrylate; and polyvinyl benzenes, such as polystyrene and polyvinyloluene. Polyvinyl chloride is particularly emphasized.

For the preparation of the molded bodies based on polyvinyl resin are suitable plasticizers which are usually used to plasticize solid vinyl resins. The plasticizer to be used depends on the resin and its compatibility with the plasticizer. Suitable plasticizers are, for example, phosphoric acid esters, such as phthalic acid esters, such as dimethyl phthalate and dioctyl phthalate, and adipic acid esters such as diisobutyl adipate. Other esters may also be used, such as esters of azelaic acid, maleic acid, ricinoleic acid, myristic acid, palmitic acid, oleic acid, sebacic acid, stearic acid and trimellitic acid, as well as complex linear polyesters, polymeric plasticizers and soybean oils epoxidized. The amount of the plasticizer amounts to about 10 to 50% by weight, preferably about 20 to 45% by weight of the total composition.

In the molded bodies there may further be contained additional components, such as stabilizing agents, slip agents, fillers and coloring materials, without thereby altering the basic properties of the composition. Suitable stabilizing agents are the antioxidant agents and agents that protect the bands from ultraviolet radiation and unwanted degradation during processing, such as extrusion presses. Some stabilizing agents, such as epoxidized soybean oils, further serve as secondary plasticizers. Sliding agents can be used, for example, stearates, stearic acid and low molecular weight polyethylenes. These components may be used in a concentration of up to about 5% by weight of the total composition.

In the preparation of the moldings based on vinyl the different components are mixed according to known processes and are compression molded according to known processes of extrusion pressing or injection molding. The selection of the processing procedure for the preparation of the molded bodies is governed, in technical terms, mainly according to the rheological properties of the web material and according to the shape of the desired web. The processing procedures may be adjusted according to the processing technology or according to the type of the configuration. In the case of processing technology, the processes can be subdivided according to the rheological conditions that follow. Accordingly, for viscous web materials, molding, pressing, injection molding and application are considered, and for elasto-viscous polymers, injection molding, extrusion pressing, calendering, rolling and, where appropriate, beading Classified according to the type of the configuration, the shaped bodies according to the invention can be prepared by pouring, dipping, pressing, injection molding, extrusion, calendering, coining, deep drawing, etching.

These processing procedures are known and do not require any more detailed clarifications. In principle, the explanations given above by way of example for polyvinyl resins are valid for other polymers.

Polyurethanes which serve as the carrier material are prepared in a manner known per se by reaction of polyisocyanates with high molecular weight compounds having at least two isocyanate-reactive groups as well as optionally low molecular weight chain stretching agents and / or monofunctional chain stop agents.

As starting components in the preparation of the polyurethanes are considered the aliphatic, cycloaliphatic, araliphatic, aromatic and heterocyclic polyisocyanates, as described e.g. ex. by W. Siefken in Liebig's Annalen der Chemie, 562, pages 75 to 136. By way of example are indicated: ethylene diisocyanate, 1,4-tetramethylene diisocyanate, 1,6-hexamethylene diisocyanate, 1,12- dodecane, cyclobutane 1,3-diisocyanate, cyclohexane 1,3- and 1,4-diisocyanate, as well as any mixtures of these compounds, 1-isocyanato-3,3,5-trimethyl-5-isocyanatomethylcyclohexane (see documents DE-AS 202785 and US-PS 3401190), 2,4- and 2,6-hexahydro-toluylene diisocyanate, as well as any mixtures of these compounds; hexahydro-1,3- and / or -1,4-phenylene diisocyanate, perhydro-2,4 'and / or -4,4'-diphenylmethane diisocyanate, 1,3- and 1,4-diisocyanate phenylene, 2,4- and 2,6-toluylene diisocyanate, as well as any mixtures of these compounds; 2,4 'and / or 4,4'-diphenylmethane diisocyanate, naphthylene 1,5-diisocyanate, triphenylmethane triisocyanate 4,4', triisocyanate, polyphenyl polymethylene polyisocyanates, as obtained by condensation of aniline-formaldehyde and subsequent phosgenation and are described, e.g. GB-PS 874430 and 848671; sulfonylisocyanates of m- and p-isocyanatophenol according to US Pat. No. 3,454,606; perchlorinated aryl polyisocyanates, as described, e.g. DE-1157601 and US-PS 3277138; polyisocyanates having carbodiimide groups, as described in DE-PS 1092007 and US-PS 3152162; diisocyanates, as described in US-PS 3492330; polyisocyanates having allophanate groups, as described, e.g. GB-PS 994890, DE-PS 761626 and published Dutch patent application 7102524; polyisocyanates having isocyanurate groups, as described, e.g. in US-PS 3001973, DE-PS 1022789, 1222067 and 1027394, as well as DE-OSen 1929034 and 2004048; polyisocyanates having urethane groups, as described, e.g. ex. , DE-PS 752261 or in US-PS 3394164; polyisocyanates having acylated urea groups according to DE-PS 1230778; polyisocyanates having biuret groups, as described, e.g. DE-PS 1101394, US-PS Nos. 3124605 and 3201372, as well as GB-PS 889050; polyisocyanates prepared by telomerization reactions, as described, e.g. e.g., in US-PS 3654106; polyisocyanates having ester groups, as described, e.g. GB-PS Nos 965474 and 1072956, and in US-PS 3567763 and DE-PS 1231688; reaction products of the above-mentioned isocyanates with acetals according to DE-PS 1072385 and polyisocyanates containing polymeric fatty acid residues in accordance with US-PS 3455883.

It is also possible to use the distillation residues having isocyanate groups, which occur in the technical preparation of isocyanates, optionally dissolved in one or more of the previously mentioned polyisocyanates. In addition, it is possible to use any mixtures of the polyisocyanates previously indicated.

Preferred polyisocyanates are in general toluylene diisocyanates and diphenylmethane diisocyanates.

The starting components for the preparation of the polyurethanes are furthermore compounds having at least two isocyanate-reactive hydrogen atoms, with a molecular weight as a rule of 400-10,000. These are, in addition to compounds having amino groups, thiol groups or carboxyl groups, preferably polyhydroxyl compounds, in particular compounds having two to eight hydroxyl groups, in particular those having a molecular weight of 800 to 10000, preferably 1000 to 6000, e.g. ex. polyesters, polyethers, polythioethers, polyacetals, polycarbonates and polyesteramides having at least two, usually 2-8, but preferably 2-4 hydroxyl groups, as they are known per se for the preparation of homogeneous polyurethanes and cellular polyurethanes .

The polyesters having hydroxyl groups which are considered are, e.g. reaction products of polyvalent, preferably bivalent, and optionally, additionally, trivalent carboxylic acids. Instead of the free polycarboxylic acids the corresponding polycarboxylic acid anhydrides or the corresponding polycarboxylic acid esters of lower alcohols or mixtures thereof can also be used for the preparation of the polyesters. The polycarboxylic acids may be of aliphatic, cycloaliphatic, aromatic and / or heterocyclic nature and may optionally be substituted e.g. ex. with halogen and / or unsaturated atoms.

Examples for the purpose are: succinic acid, adipic acid, suberic acid, azelaic acid, sebacic acid, phthalic acid, isophthalic acid, trimellitic acid, phthalic anhydride, tetrahydrophthalic acid anhydride, hexahydrophthalic acid anhydride , tetrachlorophthalic anhydride, endomethylenetetrahydrophthalic anhydride, glutaric acid anhydride, maleic acid, maleic anhydride, fumaric acid, dimeric and trimeric fatty acids, such as oleic acid, optionally in admixture with monomeric fatty acids, dimethyl terephthalate and bis-glycol terephthalate.

As polyhydric alcohols are considered, e.g. ethylene glycol, (1,2) - and (1,3) -propylene glycol, (1,4) - and (2,3) -butyleneglycol, (1,6) -hexanediol, (1,8) - octanediol, neopentyl glycol, cyclohexanedimethanol (1,4-bis-hydroxy-methylcyclohexane), 2-methyl-1,3-propanediol, glycerol, trimethylolpropane, (1,2,6) -hexanetriol, 4) -butanetriol, trimethylethane, pentaerythritol, quinitol, mannitol and sorbitol, methylglucositol, furthermore diethyleneglycol, triethyleneglycol, tetraethyleneglycol, polyethylene glycols, dipropylene glycols, polypropylene glycols, dibutyleneglycol and polybutylene glycols. The polyesters may have partially terminal carboxyl groups. Polyesters of lactones may also be used, e.g. ex. ε-caprolactone or hydroxycarboxylic acids, e.g. ex. ω-hydroxycaproic acid.

As polyhydric alcohols, polyethers having at least two hydroxyl groups, generally two to eight, preferably two to three, may be considered. These are themselves known and are prepared, e.g. eg, by the polymerization of epoxides such as ethylene oxide, propylene oxide, butylene oxide, tetrahydrofuran, styrene oxide or epichlorohydrin with themselves, e.g. ex. in the presence of BF 3 or by adding these epoxides, optionally in admixture or successively, to starting components with reactive hydrogen atoms, such as water, alcohols, ammonia or amines, e.g. ex. ethylene glycol, (1,3) - or (1,2) -propylene glycol, trimethylolpropane, 4,4'-dihydroxy-diphenylpropane, aniline, ethanolamine or ethylenediamine. Sucrose polyethers are also contemplated, as described, e.g. DE-ASEN 1176358 and 1064938 are often preferred. Those polyethers having predominantly primary OH groups (up to 90% by weight over all OH groups present in the polyether) are often preferred. Also suitable are polyethers modified by vinyl polymer, as they are produced, e.g. by polymerization of styrene and acrylonitrile in the presence of polyethers (USPatents 3383351, 3304273, 3523093, 3110695, German Patent Publication 1152536), also polybutadienes having OH groups.

Among the polythioethers are in particular the condensation products in thiodiglycol with themselves and / or with other glycols, dicarboxylic acids, formaldehyde, aminocarboxylic acids or aminoalcohols. Depending on the respective component parts, the products are polythioethers, polythioether esters or polythioether amides.

As polyacetals are considered, e.g. Compounds which may be prepared from glycols such as diethyleneglycol, triethyleneglycol, 4,4'-dioxethoxydiphenyldimethylmethane, hexanediol and formaldehyde. Suitable polyacetals according to the invention may also be prepared by the polymerization of cyclic acetals.

As polycarbonates having hydroxyl groups are considered those which can be prepared in a manner known per se. ex. by reaction of diols such as (1,3) -propanediol, (1,4) -butanediol and / or (1,6) -hexanediol, diethyleneglycol, triethyleneglycol or tetraethyleneglycol with diaryl carbonates, e.g. ex. diphenyl carbonate or phosgene.

Among the polyesteramides and polyamides are included, e.g. eg, mainly linear condensates obtained from saturated and unsaturated polyvalent carboxylic acids or their anhydrides, and aminoalcohols, diamines, polyamines and mixtures thereof, polyhydric and saturated and unsaturated.

Polyhydroxy compounds already containing urethane or urea groups, as well as optionally modified natural polyols such as castor oil, carbohydrates or starch, may also be used. Also according to the invention may be used addition products of alkylene oxides in phenol-formaldehyde resins or also in urea-formaldehyde resins.

Representatives of these compounds are described, e.g. High Polymers, vol. XVI, Polyurethanes, Chemistry and Technology, quoted by Saunders-Frisch, Interscience Publishers, New York, London, Volume I, 1962, pages 32-42 and pages 44-54, and volume II, 1964, pages 5-6 and 198-199, as well as in the Kunststoff-Handbuch, volume VII, Vieweg-Höchtlen, Carl-Hanser-Verlag, Munich, 1966, p. ex. on pages 45-71.

Of course, mixtures of the above compounds with at least two isocyanate-reactive hydrogen atoms, having a molecular weight of 400-10000, wt. ex. mixtures of polyethers.

As starting components which may optionally be used, compounds having at least two isocyanate-reactive hydrogen atoms having a molecular weight of 32-400 are also considered. Also in this case, the compounds having the groups hydroxyl groups and / or amino groups and / or thiol groups and / or carboxyl groups, preferably compounds serving as chain extenders or crosslinking agents. These compounds generally contain 2 to 8 isocyanate-reactive hydrogen atoms, preferably 2 or 3 reactive hydrogen atoms.

As examples for compounds of this type are indicated:

Ethylene glycol, (1,2) - and (1,3) -propyleneglycol, (1,4) - and (2,3) -butyleneglycol, (1,5) -pentanediol, (1,6) -hexanediol, , 2-methyl-1,3-propanediol, glycerol, trimethylolpropane, (1,2,6) -hexanetriol, trimethylolethane, pentaerythritol, quinithiol, trimethylolpropane, mannitol and sorbitol, diethyleneglycol, triethyleneglycol, tetraethyleneglycol, polyethylene glycols having a molecular weight of up to 400, dipropylene glycol, polypropylene glycols of up to 400 molecular weight, dibutylene glycols, polybutylene glycols of up to 400, 4,4'-dihydroxy-diphenylpropane, di hydroxymethylhydroquinone, ethanolamine, diethanolamine, triethanolamine, 3-aminopropanol, ethylenediamine, 1,3-diaminopropane, 1-mercapto-3-aminopropane, 4-hydroxy-or-aminophthalic acid, succinic acid, adipic acid, hydrazine, N, N'-dimethylhydrazine, 4,4'-diaminodiphenylmethane, toluylene diamine, methylene-bis-chloraniline, methylene-bis-anthranilic acid esters, diaminobenzoic acid and the isomeric chlorophenylenediamines.

Also in this case mixtures of different compounds with at least two isocyanate-reactive hydrogen atoms having a molecular weight of 32-400 may be used.

However, polyhydroxyl compounds in which high molecular weight polyadducts or polycondensates are also present in finely dispersed or dissolved form may also be used. Modified polyhydroxy compounds of this type are obtained when polyaddition reactions (eg reactions between polyisocyanates and aminofunctional compounds) or polycondensation reactions (eg formaldehyde and phenols and / or amines) are carried out directly in situ in the compounds having hydroxyl groups mentioned above. Processes of this type are described, for example, in DE-ASen 1168 075 and 1260142, as well as in DE-OSen documents 2324134, 2423984, 2512385, 2513815, 2550797, 2550833 and 2550862. However, it is also possible, according to DE- US-PS 3869413 or DE-OS 2550860, mixing a finished aqueous polymer dispersion with a polyhydroxy compound and then removing water from the blend.

In selecting the high molecular weight polyol component used for the preparation of the polyurethane it should be noted that the finished polyurethane should not have swelling ability in water. Therefore, the use of an excess in polyhydroxy compounds with ethylene oxide units (polyether polyethylene glycol or polyester with diethyleneglycol or triethylene glycol as the diol component) should be avoided.

Thermoplastic elastomers are particularly emphasized for the preparation of molded bodies. These are materials containing elastomer phases in thermoplastic processable polymers, either chemically mixed or chemically bonded. Polymer blends are distinguished, wherein the elastomeric phases are a component of the polymeric structure. Through the assembly of the thermoplastic elastomers, there are hard zones and adjacent soft zones. The hard zones in this case form a crystalline lattice structure or a continuous phase whose interstices are filled by elastomeric segments. Due to this assembly, these materials have rubbery properties. It is possible to distinguish 5 main groups of thermoplastic elastomers: 1. Copolyesters 2. Polyether block amides (PEBA) 3. Thermoplastic polyurethanes (TPUs) 4. Thermoplastic polyolefins (TPO) 5. Styrene block copolymers

Suitable copolyesters (segmented polyester elastomers) are synthesized, for example, from a multiplicity of short chain ester units and repeating long chain ester units which are combined by ester linkages, wherein the chain ester units Short films are about 15-65% by weight of the copolymer and have formula I.

Formula I wherein R represents a bivalent residue of a dicarboxylic acid having a molecular weight of less than about 350, D represents a bivalent residue of an organic diol having a molecular weight of less than about 250,

The long chain ester moieties make up about 35-85% by weight of the copolyester and have the formula II

Formula II wherein R represents a bivalent residue of a dicarboxylic acid having a molecular weight of less than about 350, G represents a bivalent residue of a long chain glycol having an average molecular weight of about 350 to 6000.

The copolyesters usable according to the invention may be prepared by polymerizing together a) one or more dicarboxylic acids, b) one or more long chain linear glycols, and c) one or more low molecular weight diols.

The dicarboxylic acids for the preparation of the copolyester may be aromatic, aliphatic or cycloaliphatic. Preferred dicarboxylic acids are aromatic acids having 8-16 carbon atoms, in particular phenylenedicarboxylic acids, such as phthalic, terephthalic and isophthalic acid.

The low molecular weight diols for the reaction for the formation of the short chain ester units of the copolyesters belong to the class of acyclic, alicyclic and aromatic dihydroxy compounds. Preferred diols have 2-15 C atoms, such as ethylene, propylene, tetramethylene, isobutylene, pentamethylene, 2,2-dimethyltrimethylene, hexamethylene and decamethylene, dihydroxycyclohexane, cyclohexanedimethanol glycols , resorcinol, hydroquinone and the like. Bisphenols for the present purpose include bis- (p-hydroxy) diphenyl, bis (p-hydroxyphenyl) methane, bis (p-hydroxyphenyl) ethane and bis (p-hydroxyphenyl) propane.

The long chain glycols for the preparation of the soft segments of the copolyesters preferably have molecular weights of from about 600 to 3000. To these belong the poly (alkylene ether) glycols, wherein the alkylene groups have 2- 9 carbon atoms.

The glycol esters of poly (alkylene oxide) dicarboxylic acids may also find use as long chain glycol.

Polyester glycols may also find use as long chain glycol.

Long chain glycols also belong to the polyform, which are obtained by reacting formaldehyde with glycols. The polythioetherglycols are also suitable. The polybutadiene and polyisoprene glycols, the blend polymers thereof and the saturated hydrogenation products of these materials represent satisfactory long chain polymer glycols.

Methods for the synthesis of copolyesters of this type are known from DOS 2239271, DOS 2213128, DOS 2449343 and US-P 3023192.

Suitable copolyesters are obtainable e.g. ex. under the trade names "Hytrel" from Du Pont, "Toypen" from Toyobo®, Arnitel from Akzo, "Easttel Kodak" and "Riteflex" from Hoechst.

Suitable polyether block amides are for example those which are composed of polymer chains which are composed of repeating units corresponding to formula I.

Formula I wherein A is the polyamide chain derived from a polyamide with 2 carboxyl groups by loss of the latter, and B is the polyoxyalkylene glycol chain derived from a polyoxyalkylene glycol with terminal OH groups by loss of the latter, n is the number of the forming units of the polymer chain.

Terminals are, in this case, preferably OH groups or residues of the compounds which interrupt the polymerization.

The polyamides of dicarboxylic acids with the terminal carboxyl groups are obtained in known manner, e.g. ex. by polycondensation of one or more lactams and / or one or more amino acids, furthermore by polycondensation of a dicarboxylic acid with a diamine, respectively in the presence of an excess of an organic dicarboxylic acid, preferably with terminal carboxyl groups. These carboxylic acids become a component of the polyamide chain during polycondensation and are particularly positioned at the end thereof, whereby a polyamide of α-ω-dicarboxylic acid is obtained. In addition, the dicarboxylic acid acts as a chain breaking agent, whereby it is also used in excess. The polyamide may be obtained from lactams and / or amino acids having a hydrocarbon chain consisting of 4-14 C atoms, such as e.g. ex. of caprolactam, enantholactam, dodecalactam, undecanolactam, decanolactam, 11-aminoundecane or 12-aminododecanoic acid.

As examples for polyamides, as they are produced by polycondensation of a dicarboxylic acid with a diamine, the condensation products of hexamethylenediamine with adipic, azelaic, sebacic and 1,12-dodecanedioic acid can be indicated, as well as the condensation products of nonamethylenediamine and adipic acid.

In the case of the dicarboxylic acids used for the synthesis of the polyamide, that is, on the one hand, for the attachment of a carboxyl group, respectively, at each end of the polyamide chain, and on the other hand as chain breaking agents, those having 4-20 C atoms, in particular the alkanedioic acids, such as succinic, adipic, suberic, azelaic, sebacic, undecanedioic or dodecanedioic acids, in addition to cycloaliphatic or aromatic dicarboxylic acids such as terephthalic or isophthalic acid or cyclohexane- 1,4-dicarboxylic acid.

The polyoxyalkylene glycols having terminal OH groups are unbranched or branched and have an alkylene residue having at least 2 C atoms. These are, in particular, polyoxyethylene glycol, polyoxypropylene glycol and polyoxytetramethylene glycol, as well as copolymerizates thereof. The average molecular weight of these OH-terminated polyoxyalkylene glycols can range from a large range, advantageously from 100 to 6000, in particular from 200 to 3000. The weight ratio of the polyoxyalkylene glycol to the total weight of the polyoxyalkylene glycol and the dicarboxylic acid polyamide used for the preparation of PEBA polymers, makes up 5 - 85%, preferably 10 - 50%.

Methods for the synthesis of PEAB polymers of this type are known from FR-PS 7418913 (N1 233 of publication 2273021), DOS 2802989, DOS 2837687, DOS 2523991, EP-S 0095893, DOS 2712987 or DOS 2716004.

Preferably, those PEBA polymers which, as opposed to those described above, are synthesized are statistically suitable. For the preparation of these polymers, a mixture of 1 or more polyamide-forming compounds of the group of the ω-aminocarboxylic acids or lactams having at least 10 carbon atoms, a α-ω-dihydroxy-polyoxyalkylene glycol, at least one organic dicarboxylic acid in a weight ratio of 1: (2 + 3) between 30:70 and 98: 2, wherein in (2 + 3) hydroxyl groups and carbonyl groups are present in equivalent amounts, in the presence of 2 to 30 parts by weight of percent by weight of water relative to the polyamide-forming group 1 compounds under the preset pressure is heated to temperatures between 23 ° C and 30 ° C, and then, after removal of the water to the exclusion of oxygen under normal pressure or under reduced pressure, it is reacted at 250 to 280 ° C.

PEAB polymers of this type, suitably suitable, are described e.g. ex. in DE-OS 2712987.

Suitable and suitable PEAB polymers are preferably obtained e.g. ex. under the tradenames ®PEBAX from Atochem, ®Vestamid from Hills AG, ®Glamamid from EMS-Chemie and ®Kellaflex from DSM.

The shaped bodies contain the active substance in concentrations of 1 to 20% by weight, preferably 5 to 20% by weight, preferably in particular 10% by weight.

In the case of collars, the concentration of the active substances is preferably in 1 to 15%; in the case of medallions, pendants or ear tags, is preferably 5 to 20%, in the case of sheets, adhesive tapes, it is preferably in 0.1 to 5%. Imidacloprid is in combination with synthetic pyrethroids, flumethrin (3- [2- (4-chlorophenyl) -2-chlorovinyl] -2,2-dimethyl-cyclopropanoic acid [(α-cyano-4-fluoro- 3-phenoxy) -benzyl] ester) or permethrin (3-phenoxybenzyl (+) - cis, trans-3- (2,2-dichlorovinyl) -2,2-dimethylcyclopropane carboxylate).

The molded bodies may additionally contain the usual additives for synthetic materials. Usual additives are for example pigments, stabilizers, flow agents, lubricating agents, demoulding agents.

Imidacloprid is employed in the following examples. These are not examples according to the invention, since no mixture of imidacloprid is used therein with flumethrin or permethrin. However, they provide a technological basis for the application of imidacloprid.

Example 1

Formulation SC (suspension concentrate): 368 g of imidacloprid 35 g of block polymer of emulsifier ethylene oxide and propylene oxide 12 g of dithiolylether formaldehyde sulfonate condensate (emulsifier) 3.5 g of water-soluble polyvinyl alcohol 58.0 g of Nh4cl 116.0 g of urea 1.2 g of (37% aqueous hydrochloric acid) 4.6 g of xanthan gum 560.5 g of distilled water

Formulation WP (dispersible powder):

Example 2 25.0 g of imidacloprid 1.0 g of sodium diisobutyl naphthalene sulfonate 10.0 g of calcium n-dodecylbenzenesulfonic acid 12.0 g of alkylaryl polyglycol ether containing highly dispersed silicon acid 3.0 g of dithiolylether formaldehyde sulfonate condensate (emulsifier) 2.0 g ®Baysilon-E, an antifoaming agent containing

Silicon from Bayer AG 2.0 g of finely dispersed silicon dioxide, and 45.0 g of kaolin

Example 3

Formulation SL (water-soluble concentrate) 18.3 g of imidacloprid 2.5 g of neutral emulsifier based on alkylaryl polyglycol ether 3.5 g of sodium diisooctyl sulfosuccinate 38.4 g of dimethylsulfoxide and 37.5 g of 2-propanol

Example 4

Formulation SL (water-soluble concentrate) 185 g imidacloprid 5.0 g sodium diisooctyl sulfosuccinate 76.5 g dimethylsulfoxide are mixed in a 100 g shampoo formulation composed of

44.4% by weight of Marlon AT 50, a triethanolamine salt of alkylbenzenesulfonic acids from Huls AG

11.1 wt.% Of Marlon A 350, sodium salt of alkylbenzenesulfonic acids of Huls AG 3.0 wt.% Of condensation product of oleic acids and diethanolamine of Huls AG, and 41.5 wt.% Of polyethylene glycol.

Example 5

Spray formulation composed of 2.0 g of imidacloprid 10.0 g of dimethylsulfoxide 35.0 g of 2-Propanol, and 53.0 g of acetone

Example 6

Spray formulation 20.3 g imidacloprid 1.8 g polyvinyl alcohol 1.8 g block copolymerized ethylene oxide and propylene oxide 0.26 g xanthan gum 9.0 g glycerol 59.2 g water distilled

Example 7

Composition: Imidacloprid 10.00 g

Di-n-butyl adipate 21.10 g

Diethylhexyl phthalate 9.10 g Epoxidized soybean oil 2.30 g Stearic acid 0.80 g PVC 56.70 g

Preparation: The homogeneous mixture of imidacloprid and PVC is moistened in a blender with the mixture of di-n-butyl adipate, diethylhexyl phthalate and epoxidized soybean oil. Mix the necessary time until the mixture is homogeneous. In this case, heating, e.g. ex. as a consequence of an increase in the number of rotations of the mixer, promotes the introduction of the plasticizer mixture into the PVC. After the subsequent homogeneous distribution of stearic acid, the blend is injection molded to form dog collars.

Example 8

Composition: Imidacloprid 10.00 g Epoxidized soybean oil 2.30 g Stearic acid 0.80 g

Acetyltributyl citrate 30.20 g PVC 56.70 g

Preparation: The mixture of acetyltributyl citrate and epoxidized soybean oil is placed in a blender on the homogeneous mixture of imidacloprid and PVC. With the mixture, the heating promotes the introduction of the plasticizer mixture into the PVC; the time required is mixed until the mixture is homogeneous. The blend is extruded in a conventional manner to form dog collars.

Example 9

Composition: Imidacloprid 20.00 g Epoxidized soybean oil 2.30 g Stearic acid 0.80 g

Acetyltributyl citrate 30.20 g PVC 56.70 g

Preparation: As example 8

Example 10

Composition: Imidacloprid 7.50 g Epoxidized soybean oil 10.00 g Stearic acid 0.80 g

Acetyltributyl citrate 15.00 g PVC 66.70 g

Preparation: As example 8

Example 11

Composition: Imidacloprid 10.00 g Epoxidized soybean oil 2.30 g Stearic acid 0.80 g

Triacetin 15.00 g PVC 71.90 g

Preparation: The mixture of triacetin and epoxidized soybean oil is placed in a blender on the homogeneous mixture of PVC and imidacloprid. In this case, heating, e.g. ex. as a consequence of an increase in the number of rotations of the mixer, promotes the introduction of the plasticizer mixture into the PVC. After the homogeneous mixture of stearic acid, the blend is extruded into an extruder to form plates, from which medallions (= pendants for collars) are printed.

Example 12

Composition: Imidacloprid 5.00 g

Amide in polyether block (Pebax) ® 94.50 g

Preparation: The active substance is placed on the carrier in an intensive blender and the blend is injection molded to form dog collars.

Example 13

Composition: Imidacloprid 10.00 g

Medium chain triglycerides 15.00 g

Highly dispersed silicon dioxide 0.50 g

Amide in polyether block (Pebax) ® 74.50 g

Preparation: Medium chain triglycerides are placed in a mixer on the homogeneous mixture of imidacloprid and polyether block amide. In this case, the heating promotes the introduction of the medium chain triglycerides into the polyether amide block. To improve flowability, highly dispersed silicon dioxide is homogeneously mixed prior to extrusion of the blend. Plates are extruded, from which medallions are printed (= pendants for collars).

Example 14

Composition: Imidacloprid 10.00 g

Block copolymer of styrene butylene (Thermoplast®K) 90.00 g

Preparation: The active substance is placed on the carrier in an intensive blender and the blend is injection molded to form dog collars.

Example 15

Composition: Imidacloprid 5.00 g

Copolyester (Hytrel®) 95.00 g

Preparation: The blend is extruded in a conventional manner to form dog collars.

Example 16

Composition: Imidacloprid 10.00 g

Amide in polyether block (Pebax) ® 90.00 g

Preparation: The homogeneous mixture is extruded into an extruder to form plates, from which medallions (= pendants for collars) are printed.

Example 17

Composition: Imidacloprid 10.00 g

Medium chain triglycerides 30.00 g

Highly dispersed silicon dioxide 0.50 g

Amide in polyether block (Pebax) ® 59.50 g

Preparation: As example 13

Example A

1 ml of the SC formulation indicated in Example 1 was applied as a solution pouring onto the back of a dog infested with 200 fleas. The experiment animal might be immediately freed from adult fleas. The treatment according to the invention leads to a 100% mortality rate of the fleas.

Application example A

1 ml of the formulation described in Example 1 was diluted in 1 L of water and dogs were infested with fleas with this solution. The following results were obtained:

Application example B

1 ml of the formulation according to example 1 was placed on the back of a dog. The animal was infested with 200 fleas after 2 days and after 6 days of treatment. Respectively on day 3 and day 7 after treatment were counted the remaining fleas on the dog. We could not find any live fleas. The effect was 100%.

Lisbon, March 19, 2015

Claims (1)

Use of imidacloprid (= 1 - [(6-chloro-3-pyridinyl) methyl] -N-nitro-2-imidazolidinimine) for the preparation of non-systemic fighting agents against parasitic insects of the flea, lice group and flies in humans and animals in combination with the synthetic pyrethroids flumethrin or permethrin. Lisbon, March 19, 2015